RGD Reference Report - Mutational profiling of therapy-related myelodysplastic syndromes and acute myeloid leukemia by next generation sequencing, a comparison with de novo diseases.

General

Mutational profiling of therapy-related myelodysplastic syndromes and acute myeloid leukemia by next generation sequencing, a comparison with de novo diseases.
Authors:	Ok, CY Patel, KP Garcia-Manero, G Routbort, MJ Fu, B Tang, G Goswami, M Singh, R Kanagal-Shamanna, R Pierce, SA Young, KH Kantarjian, HM Medeiros, LJ Luthra, R Wang, SA
Citation:	Ok CY, etal., Leuk Res. 2015 Mar;39(3):348-54. doi: 10.1016/j.leukres.2014.12.006. Epub 2014 Dec 20.
RGD ID:	11075071
Pubmed:	PMID:25573287 (View Abstract at PubMed)
PMCID:	PMC5548131 (View Article at PubMed Central)
DOI:	DOI:10.1016/j.leukres.2014.12.006 (Journal Full-text)
In this study we used a next generation sequencing-based approach to profile gene mutations in therapy-related myelodysplastic syndromes (t-MDS) and acute myeloid leukemia (t-AML); and compared these findings with de novo MDS/AML. Consecutive bone marrow samples of 498 patients, including 70 therapy-related (28 MDS and 42 AML) and 428 de novo (147 MDS and 281 AML) were analyzed using a modified-TruSeq Amplicon Cancer Panel (Illumina) covering mutation hotspots of 53 genes. Overall, mutation(s) were detected in 58.6% of t-MDS/AML and 56.8% of de novo MDS/AML. Of therapy-related cases, mutations were detected in 71.4% of t-AML versus 39.3% t-MDS (p=0.0127). TP53 was the most common mutated gene in t-MDS (35.7%) as well as t-AML (33.3%), significantly higher than de novo MDS (17.7%) (p=0.0410) and de novo AML (12.8%) (p=0.0020). t-AML showed more frequent PTPN11 but less NPM1 and FLT3 mutations than de novo AML. In summary, t-MDS/AML shows a mutation profile different from their de novo counterparts. TP53 mutations are highly and similarly prevalent in t-MDS and t-AML but mutations in genes other than TP53 were more frequent in t-AML than t-MDS. The molecular genetic profiling further expands our understanding in this group of clinically aggressive yet heterogeneous myeloid neoplasms.

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Term	Qualifier	Evidence	With	Reference	Notes	Source	Original Reference(s)
acute myeloid leukemia	treatment	IAGP		11075071	DNA:mutations: :	RGD
acute myeloid leukemia	treatment	ISO	TP53 (Homo sapiens)	11075071; 11075071	DNA:mutations: :	RGD
myelodysplastic syndrome	treatment	IAGP		11075071	DNA:mutations: :	RGD
myelodysplastic syndrome	treatment	ISO	TP53 (Homo sapiens)	11075071; 11075071	DNA:mutations: :	RGD

Objects Annotated

Genes (Rattus norvegicus)

Tp53 (tumor protein p53)

Genes (Mus musculus)

Trp53 (transformation related protein 53)

Genes (Homo sapiens)

TP53 (tumor protein p53)

Additional Information

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Mutational profiling of therapy-related myelodysplastic syndromes and acute myeloid leukemia by next generation sequencing, a comparison with de novo diseases.